Abstract: The present invention relates to methods for reducing or eliminating the expression of a target gene in a filamentous fungal strain, comprising: (a) inserting into the genome of the filamentous fungal strain a double-stranded transcribable nucleic acid construct comprising a first nucleotide sequence comprising a promoter operably linked to a homologous coding region of the target gene and a second nucleotide sequence comprising the homologous coding region, or a portion thereof, of the target gene, wherein the first and second nucleotide sequences are complementary to each other and the second nucleotide sequence is in reverse orientation relative to the first nucleotide sequence; and (b) inducing production of an interfering RNA encoded by the double-stranded transcribable nucleic acid construct by cultivating the filamentous fungal strain under conditions conducive for production of the interfering RNA; wherein the interfering RNA interacts with RNA transcripts of the target gene to reduce or eliminate exp

Abstract: A method for providing antisense therapy which reduces the expression of clusterin to provide therapeutic benefits in the treatment of cancer comprising administering from 40 to 640 mg anti-clusterin antisense oligonucleotide to a patient in need of treatment for a cancer expressing clusterin is provided. The method may include administering chemotherapeutic agent or agents, radiotherapy, and/or hormone ablation therapy. The invention also encompasses pharmaceutical compositions formulated to provide a dosage of 40 to 640 mg, and use of antisense in formulating a medicament.

Abstract: Described herein are oligonucleotides that target the human endogenous retrovirus-9 (ERV-9) long terminal repeat (LTR). The ERV-9 LTR oligonucleotides specifically hybridize with either the coding strand or non-coding strand of ERV-9 LTR. It is disclosed herein that ERV-9 LTR oligonucleotides inhibit the proliferation of cancer cells, including breast cancer, liver cancer, prostate cancer, fibrosarcoma and myeloid cancer cells. Also described herein are methods of treating a subject diagnosed with cancer comprising administering to the subject an ERV-9 LTR oligonucleotide. In some examples, the methods further comprise administering a second therapeutic agent, such as an antisense compound or a chemotherapeutic agent.

Abstract: The present invention provides a method of treating pancreatic cancer by inhibiting the activity cyclin D1 activity in tumor cells. The invention is based on the finding that cyclin D1 shRNA molecules are capable of attenuating tumor growth and interfering with tumor angiogenesis.

Abstract: Efficient sequence specific gene silencing is possible through the use of siRNA technology. By selecting particular siRNAs by rational design, one can maximize the generation of an effective gene silencing reagent, as well as methods for silencing genes. Methods, compositions, and kits generated through rational design of siRNAs are disclosed.

Abstract: A method for screening cells with high level expression of a target protein is disclosed. The method includes introducing into a plurality of host cells a DNA construct that encodes both a target protein and an inhibitor to an endogenous selectable marker in the host cells, screening host cells harboring the DNA construct for the expression of the endogenous selectable marker, and isolating cells with reduced expression of the selectable marker. Also disclosed is a DNA construct configured to express both the target protein and the inhibitor inside the host cell.

Abstract: An aptamer specifically binding to C-reactive protein (CRP) is provided. The aptamer includes a following nucleotide sequence: 5?-angngggngnntgnnt-3?, wherein n is a nucleotide selected from a, t, c and g.

Abstract: The invention provides chemically modified siRNA oligonucleotides that target RTP801L, compositions comprising same and to the use of such molecules to treat, inter alia, respiratory diseases including acute and chronic pulmonary disorders, eye diseases including glaucoma and ION, microvascular disorders, angiogenesis- and apoptosis-related conditions, and hearing impairments.

Abstract: Provided are methods and compositions, including topical compositions, for inducing tolerance to a sensitizing agent known to provoke contact hypersensitivity in a subject. Included are methods of topically applying to the subject an effective amount of an antisense composition targeting the start site or splice site of a CFLAR mRNA.

Abstract: The present invention shows that levels of certain micro RNAs (MiRNAs) are altered in NF1 cell lines and NF1 tumor cell lines as compared to non-NF1 controls. Methods are provided, e.g., to diagnose NF1 and NF1 tumors. Methods are also provided to treat NF1, NF1 related cancer, and cognitive deficits resulting from NF1.

Abstract: Disclosed herein are sequences, molecules and methods used to suppress the expression of HD genes encoding for huntingtin protein in primates including Macaca mulatto and Homo sapiens. These sequences, molecules and methods aid in the study of the pathogenesis of HD and can also provide a treatment for this disease.

Abstract: Compounds, compositions and methods are provided for modulating the expression and function of small non-coding RNAs. The compositions comprise oligomeric compounds, targeted to small non-coding RNAs. Methods of using these compounds for modulation of small non-coding RNAs as well as downstream targets of these RNAs and for diagnosis and treatment of disease associated with small non-coding RNAs are also provided.

Abstract: The invention relates to a method for the chemical synthesis of RNA, comprising the following steps: a) bonding to a solid support of a monomer having formula (II) in which—X1 is a dimethoxytrityl group,—X6 is H or an OAc group or OX3, in which X3 is a group having formula (A), in which X is O or S, R? is H or CH3 and R is selected from a linear or branched alkyl group at C1 to C4 and a R1—O—R2 group in which R1 is an alkyl group at C1 to C2 and R2 is a CH3 group or CH2CH2—O—CH3 or aryl; b) assembly with the monomer having formula (II) bound to the support thereof obtained in step (a) of at least one monomer having formula (III) in which X1, Bp, X3 are as defined for formula (II) and X5 is a hydrogen phosphonate monoester or phosphoramidite group, preferably a 2-cyanoethyl-N,N-diisopropylphosphoramidite group, which is used to obtain a protected single-strand RNA bound to a support.

Abstract: A method induces cancer, such as ovarian cancer, in primates for testing of therapeutic treatments and preclinical research and development. A nanoparticle delivers plasmid DNA encoding oncogenes and siRNAs for tumor suppressor genes. For example, a biocompatible polymer, chitosan, is complexed with three plasmids including one that carries the cDNA encoding RAS oncogene and two plasmids encoding siRNAs for two tumor supressor genes p53 and Rb. Laproscopic delivery of these nanoparticles to the ovaries of non-human primates causes ovarian carcinoma, which is detected one month after delivery of the nanoparticles.

Abstract: The present invention is directed to the diagnosis and treatment of diseases, preferably the inhibition of tumor growth and its progression to metastatic sites, through the inhibition of the action or production of PTHrP, its isoforms or PTHrP signalling. An aspect of the present invention is also directed to methods of inhibiting the PTHrP1-173 isoform through antagonists thereof, including monoclonal antibodies and siRNA directed there against. The invention may be applicable to many disease states, including but not limited to several types of cancer (including epithelial cancers such as breast, lung, colon, pancreatic, ovarian, prostate and squamous as well as melanoma) expressing PTHrP and its isoforms, alone or in combination with other therapeutic agents.

Abstract: A system and a method for determining an assessed carbohydrate to insulin ratio of a patient is described. The system and the method can comprise a memory component adapted for storing an initial set of values comprising at least one of a blood glucose level, a target blood glucose level, an insulin sensitivity, and, an estimated carbohydrate to insulin ratio. The system and the method can also comprise a bolus selection component adapted for selecting a test bolus corresponding to the determined initial set of values and a planned meal. In one implementation, the bolus selection component can receive bolus dose input from a user. In another implementation, the bolus selection component can estimate the bolus dose using a set of available inputs (e.g. the amount of carbohydrates in the planned meal). The system and the method can further comprise a user interface component adapted for receiving a confirmation that the test bolus has been administered to the patient.

Abstract: Provided are compositions and methods for therapy of macular degeneration including dry age-related macular degeneration (dAMD), juvenile macular degenerations (JMDs) where toxic retinoids are known to accumulate as part of the pathogenesis, such as Stargardt disease, and Best disease, and neovascular wet age-related macular degeneration. The method entails administering to an individual in need of therapy for macular degeneration a first polynucleotide that can facilitate a reduction in the amount of rod opsin (RHO) mRNA in the individual; or a second polynucleotide that can facilitate a reduction in the amount of RPE65 mRNA in the individual; or a combination thereof. The polynucleotides of the invention are hammerhead ribozymes or shRNAs. The polynucleotides target a sequence in RHO mRNA or RPE65 mRNA and facilitate reduction in the target mRNA via ribozymatic cleavage of the target, or by hybridization to the target, which leads to RNAi mediated degradation of the target mRNA.

Abstract: The presently disclosed subject matter provides methods and compositions for modulating gene expression in myocytes. Also provided are cells comprising the compositions of the presently disclosed subject matter.

Abstract: The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of FC?R1? gene expression and/or activity, and/or modulate a FC?R1? gene expression pathway. Specifically, the invention relates to doublestranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against FC?R1? gene expression.

Abstract: Short interfering ribonucleic acid (siRNA) for oral administration, said siRNA comprising two separate RNA strands that are complementary to each other over at least 15 nucleotides, wherein each strand is 49 nucleotides or less, and wherein at least one of which strands contains at least one chemical modification.